rs6983267

This study identified 402 m6A-associated SNPs in colorectal cancer using genome-wide association study data integrated with expression quantitative trait loci analysis. Three key SNPs were validated: rs178184 in NOVA1 (p=3.41×10⁻¹¹, downregulated), rs35782901 in HTR4 (p=5.56×10⁻⁷, downregulated), and rs60571683 in SLCO1B3 (overexpressed, p=1.09×10⁻⁶ to 7.63×10⁻⁶), suggesting these m6A-SNPs may influence colorectal cancer pathogenesis through altered gene expression.

This study applied three epistasis detection algorithms (BOOST, FastEpistasis, and TEAM) to a colorectal cancer GWAS dataset (603 cases, 457 controls) from Newfoundland and Labrador to identify gene-gene interactions. The analysis identified 251 unique SNPs in pairwise interactions, with key hub SNPs rs2412531, rs349699, rs17142011, and others mapping to 58-62 genes. Known CRC-associated genes (MACF1, USP49, SMAD2, SMAD3, TGFBR1, RHOA) were rediscovered, and CCDC32 was identified as a novel potential CRC risk factor.

This integrative genomic study identified 402 m6A-associated SNPs related to colorectal cancer by combining GWAS data with expression quantitative trait loci (eQTL) analysis. Three SNPs showed strong associations with altered gene expression: rs178184 in NOVA1 (p=3.41×10⁻¹¹, downregulated), rs35782901 in HTR4 (p=5.56×10⁻⁷, downregulated), and rs60571683 in SLCO1B3 (p=7.63×10⁻⁶, upregulated in CRC tissues), suggesting these m6A-SNPs may influence colorectal cancer pathogenesis through altered mRNA modification.

Case-control study of 459 gastric cancer patients and 379 controls in a Korean population examined the association between HULC rs7763881 polymorphism and gastric cancer risk. Overall analysis showed no significant association, but stratified analysis revealed that the CC genotype was significantly associated with increased risk in undifferentiated gastric cancer (OR = 1.85, 95% CI = 1.17–2.94, P = 0.009), diffuse-type GC (OR = 1.72, 95% CI = 1.05–2.82, P = 0.033), lymph node metastasis-positive tumors (OR = 2.02, 95% CI = 1.24–3.27, P = 0.004), and advanced tumor stages.

Fine mapping analysis of the BARD1 locus (2q35) identified two independent functional SNPs associated with high-risk neuroblastoma: rs17489363 (C>T, OR=1.79, P=1.07×10⁻³¹) in the promoter region correlating with low full-length BARD1 expression, and rs1048108 (G>A, OR=0.65, P=7.27×10⁻¹⁴). Functional studies demonstrated that full-length BARD1 acts as a tumor suppressor, with low expression associated with aggressive neuroblastoma phenotype.

This study analyzes 243 rectal cancer patients to determine if colorectal cancer (CRC) susceptibility SNPs are associated with rectal cancer prognosis. SNPs on 8q24 (rs6983267 near MYC), 18q21 (rs12953717, rs4464148 in SMAD7), and 20q13 (rs4925386 in LAMA5) are found to be associated with disease-free survival and overall survival in rectal cancer patients, with some alleles associated with better or worse prognosis despite their effects on CRC risk.

This case-control study in Japanese population evaluated CRC risk prediction models using SNPs identified in European and East Asian GWAS. An 11-SNP model combining 6 European-identified SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) with 5 East Asian-identified SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) showed significantly improved discrimination capacity compared to a 6-SNP model alone (derivation AUC 0.6392 vs 0.6125, P=0.0039; replication AUC 0.5695 vs 0.5310, P=0.0018), with cumulative risk at age 80 estimated at 13% in high-risk versus 6% in low-risk genetic groups.

This case-control study examined the association between West African ancestry (WAA) and prostate cancer (PCa) risk and aggressiveness in 291 Puerto Rican (PR) and 200 African American (AA) cases versus 133 PR and 207 AA controls. The SNP rs7824364 at chromosome 8q24 was significantly associated with PCa in both populations (p<0.0001 for AA, p=0.0001 for PR), with 82% of AA cases and 41% of PR cases carrying 1-2 risk alleles. Among PR men, those with the rs7824364 risk allele showed elevated WAA (39% versus 29%, p=0.034). No direct association between WAA and PCa aggressiveness was found.

This genome-wide association study of 2511 familial prostate cancer cases and 1382 controls identified significant associations in six regions previously linked to prostate cancer risk. Most notably, rs138042437 at 8q24.21 achieved an exceptionally large effect size (OR=13.3, p=1.7e-8) and demonstrated strong co-segregation with disease in 116 affected relatives (p=8.5e-11). The study identified a rare segregating haplotype at 8q24.21 containing three SNPs (rs183373024, rs188140481, rs138042437) that characterized a prostate cancer predisposition locus.

A three-stage fine mapping study of the 3q28 bladder cancer susceptibility locus identified rs35592567 in the 3'-UTR of TP63 as a functional causal variant. The T allele was significantly associated with decreased bladder cancer risk (OR=0.82, 95% CI=0.75-0.90, P=9.797×10⁻⁶). Functional studies showed the variant affects miR-140-5p binding, regulating TP63 post-transcriptional levels and affecting bladder cancer cell proliferation, migration, and invasion.

This case-control study of 543 endometrial carcinoma patients and 584 controls found that the rs6983267 G allele at 8q24.21 was significantly associated with increased endometrial cancer risk (OR=1.00 for GG vs 0.74 for GT+TT; p=0.021). The study identified upregulation of CARLo-5 long non-coding RNA in EC tissues and demonstrated a significant correlation between rs6983267 genotype and CARLo-5 expression (p<0.05). High CARLo-5 expression was associated with advanced FIGO stage (p=0.029), lymph node metastasis (p=0.030), and poor overall survival (p=0.003).

A case-case association study of 18,343 prostate cancer patients (16,515 European, 1,828 African-American) evaluating 36 validated PC-risk SNPs found that rs2735839 (G allele) on chromosome 19q13 in the KLK3 gene was significantly and inversely associated with aggressive disease and high Gleason scores in both populations (p = 9.343 × 10⁻⁸ overall, p = 1.042 × 10⁻⁵ European, p = 2.0 × 10⁻⁴ African-American).

Developed a multi-state genetic variant-based Markov model for personalized prostate cancer risk stratification using Finnish population data. The model incorporates three primary SNPs (rs4242382 OR=1.75, rs138213197 OR=3.60, rs200331695 OR=6.0) and an extended panel of genetic variants to predict 10-year PCa risk ranging from 43% in the top 5% risk group to 11% in the bottom 60%, with recommendations for age-optimized screening (47 years for highest risk vs 55+ years for average/low risk) and risk-adapted interscreening intervals (< 1 year to 6+ years).

This genome-wide association study (GWAS) of gene-by-environment interactions examined 8,634 colorectal cancer cases and 8,553 controls to identify genetic variants that modify the protective effect of aspirin and NSAIDs against colorectal cancer. Regular aspirin/NSAID use was associated with reduced colorectal cancer risk (OR=0.69, 95% CI=0.64-0.74). Two SNPs showed genome-wide significant interactions: rs2965667 near MGST1 (P=4.6×10⁻⁹) provided protection in TT carriers (OR=0.66) but increased risk in TA/AA carriers (OR=1.89); rs16973225 near IL16 (P=8.2×10⁻⁹) provided protection in AA carriers (OR=0.66) but not in AC/CC carriers (OR=0.97).

This functional study investigated the cancer-associated SNP rs61764370 (T>G) in the 3' UTR of KRAS using site-specific homologous recombination to knock-in the variant in colorectal cancer cells (SW48). The study found that the rs61764370 variant increased cellular proliferation approximately two-fold and reduced let-7a, let-7b, and let-7c microRNA levels by 1.6-fold (P<0.05), but had no effect on KRAS protein expression or downstream signaling (MAPK/PI3K/AKT), suggesting the variant affects cancer risk through let-7 microRNA regulation rather than KRAS transcriptional modulation.

A meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls) found that the rs6983267 polymorphism on chromosome 8q24 was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95% CI=1.13-1.26; recessive: OR=1.19, 95% CI=1.14-1.25; homozygous: OR=1.31, 95% CI=1.23-1.40). Stratified analyses showed significant associations for colorectal cancer, prostate cancer, and thyroid cancer in Caucasians, and lung cancer in Asians.

Meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls, 170,737 total subjects) examining the association between 8q24 rs6983267 G/T polymorphism and cancer susceptibility. The G risk allele was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95%CI=1.13-1.26; recessive: OR=1.19, 95%CI=1.14-1.25; homozygous: OR=1.31, 95%CI=1.23-1.40). Significant associations were found for colorectal cancer, prostate cancer, thyroid cancer, and lung cancer in ethnicity-stratified analyses.

A candidate region association study of 10 previously reported 8q24 SNPs in African-Barbadian men from the Prostate Cancer in a Black Population (PCBP) study found one significant association with prostate cancer. Rs2124036 homozygous C/C genotype showed significant association with prostate cancer risk (OR = 2.7, 95% CI 1.3-5.3, P = 0.005). Meta-analysis across three Caribbean populations (Barbados, Jamaica, Tobago) for rs16901979 and rs1447295 identified rs16901979 A allele as significantly associated (Z = 2.73, p = 0.006, OR = 1.31, 95% CI 1.09-1.58).

This case-control study evaluated rare copy number variants (CNVs), protein-truncating variants, and missense mutations in DNA damage response genes for breast cancer association in Finnish cohorts. CYP2C19 deletion showed enrichment in triple-negative breast cancer (p=0.021). TEX15 c.7253dupT frameshift variant associated with hereditary breast cancer (p=0.018). FANCD2 c.2715+1G>A splice-site variant (rs201811817) showed 7.5-fold increased risk (p=0.036, OR=7.5). RECQL p.Ile156Met and POLG p.Leu392Val (rs145289229) missense variants also associated with breast cancer (p=0.043 and p=0.010, OR=2.1 respectively).

Genome-wide investigation of gene-environment interactions in colorectal cancer using a two-tiered case-only/case-control design. In 314 sporadic CRC cases (stage I) and 259 familial CRC cases plus 1,002 controls (stage II), rs1944511 showed a significant interaction with overweight (OR=2.00, p=0.042 after multiple testing correction). Several other SNPs showed nominally significant G×E interactions with overweight, smoking, and alcohol consumption. Among candidate CRC-associated SNPs, rs9929218 showed the strongest interaction with alcohol consumption (nominal p=0.008).

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

A meta-analysis of 80 studies (69 publications) with 26,428 cancer cases and 43,381 controls evaluating the ESR1 PvuII rs2234693 T>C polymorphism and cancer susceptibility. Overall, the T allele showed modest decreased cancer risk (OR=0.95, 95% CI=0.91-0.99), with stronger associations for specific cancer types: prostate cancer (TT vs. CC: OR=0.79), leiomyoma (T vs. C: OR=0.82), and hepatocellular carcinoma (TT vs. CC: OR=0.45). The authors conclude that ESR1 PvuII polymorphism has minimal impact on overall cancer susceptibility.

This study demonstrates that 13 of 14 previously identified prostate cancer risk SNPs are significantly associated with early-onset prostate cancer (EO PCa; diagnosed ≤55 years), with effect sizes ranging from OR=1.15 to OR=1.55 per risk allele. Early-onset cases carried significantly more cumulative risk alleles (mean 12.4) compared to older-onset CGEMS cases (mean 11.9; p=1.7×10⁻⁵), suggesting common genetic variants play an increased role in earlier disease manifestation.

This study examined 10 chromosome 8q24 SNPs in 1,157 men (308 prostate cancer cases, 469 controls from West Africa, and additional Caribbean and population samples) to determine the prevalence and risk magnitude of 8q24 variants in populations of African descent. The study replicated associations between prostate cancer risk and rs6983561 (OR=0.6, P=0.03), rs16901979 (OR=1.6, P=0.03), and rs7008482 (OR=2.3) in West African men, with no significant heterogeneity of effects across African descent populations.

Analysis of 20 GWAS-identified prostate cancer susceptibility SNPs in 601 patients treated with androgen-deprivation therapy (ADT) found that rs16901979 at 8q24 was significantly associated with prostate cancer-specific mortality (HR = 0.63, 95% CI 0.45-0.87, p = 0.005) and rs7931342 at 11q13 was associated with mortality (HR = 0.65, 95% CI 0.43-0.98, p = 0.038). These variants may help predict survival outcomes in prostate cancer patients undergoing ADT treatment.

Meta-analysis of genome-wide association studies examining colorectal cancer susceptibility in 2,906 cases and 3,416 controls (GWAS) with replication in 8,161 cases and 9,101 controls. Eight of ten previously identified SNPs showed associations (p-values 0.02 to 1.8×10⁻⁸), and the study identified marginal evidence for a second independent signal in BMP2 (rs4813802, combined p=7.3×10⁻⁵) and a novel association with TERT-CLPTM1L (rs2853668, combined p=1.9×10⁻⁴).

This case-control study evaluated 157 tag SNPs in the 8q24 chromosomal region in relation to papillary thyroid cancer (PTC) risk using 344 PTC cases and 452 controls. While previously cancer-associated SNPs (rs1562430, rs1447295, rs6983267) showed no significant association with PTC, one SNP (rs4733616, P=0.003) and 12 others showed uncorrected P<0.05 associations; however, none remained significant after false discovery rate correction, suggesting no strong association between 8q24 variants and sporadic PTC risk.

A case-control study of 489 prostate cancer cases and 427 controls in a New Zealand Caucasian population examined 15 chromosome 8q24 SNPs. Four SNPs showed statistically significant associations with prostate cancer risk: rs10086908 (T allele, OR=1.64), rs16901979 (A allele, OR=2.58), rs1447295 (A allele, OR=1.70), and rs4242382 (A allele, OR=1.60). A weighted genetic risk score based on all 15 SNPs was significantly associated with prostate cancer risk (OR=1.10), with smoking contributing additional risk.

This GWAS replication study evaluated 800 SNPs in African American (n=417) and European American (n=455) prostate cancer cases versus controls (n=925 AA, n=1,687 EA) from the NC-LA Prostate Cancer Project. Of 32 European-based GWAS SNPs, 13 were significant at P<0.05 in European Americans and 4 in African Americans (rs6983267, rs7017300, rs1859962, rs6501455). Two additional SNPs reached study-wide significance: rs1472606 (OR=1.43 in EA) and rs9351265 (OR=1.48 in AA). The study confirms a large proportion of cancer-associated regions from European GWAS but shows limited predictive value (AUC=0.60 in EA, 0.56 in AA) for clinical screening.

Case-control study in 354 Tobago men with screening-detected prostate cancer and 438 controls examining associations between chromosome 8q24 variants and prostate cancer risk. SNP rs16901979 showed significantly increased prostate cancer risk (OR=1.41, 95% CI 1.02-1.95, P=0.04), with stronger association in early-onset prostate cancer (OR=2.37, 95% CI 1.40-3.99, P=0.001). SNPs rs1447295 and rs6983267 showed no overall association, but rs1447295 showed tendencies toward increased risk in early-onset cases.

This population-based case-control study evaluated 17 prostate cancer susceptibility loci identified in European GWAS populations in Chinese men (288 cases, 155 controls from Shanghai). Two of 17 loci on chromosome 8q24 showed significant associations with prostate cancer risk (rs1016343: OR=2.07, P=9.4×10⁻⁴; rs10090154: OR=2.07, P=0.002). Multiple additional SNPs at 8q24 regions 1 and 2 were also significantly associated with prostate cancer risk, while region 3 SNPs showed mostly null associations. Results suggest that prostate cancer risk variants identified in European populations are also relevant for Chinese men.

Systematic literature review of 22 GWAS studies identifying 53 SNPs in 29 genomic loci associated with aggressive and progressive prostate cancer, particularly in low-grade disease. Functional analysis of 21 SNPs revealed involvement in the MYC/POU5F1B pathway (rs1447295, rs6983267, rs4242382), androgen receptor pathway (rs17021918, rs10486567, rs7679673, rs2939244), and PSA/KLK3 biomarkers (rs2735839, rs10993994). SNPs were integrated with somatic copy number aberration data, with 17 SNPs found in regions of recurrent CNAs predictive of progression; notably, rs1447295 and 7 other SNPs cluster in 8q24 gain regions harboring MYC.

This meta-analysis of genome-wide association studies identified 30 prostate cancer risk-associated SNPs in Caucasian populations. The SNPs had odds ratios ranging from 1.12-1.47, except rs16901979 (OR=1.80). These 30 SNPs collectively explained approximately 13.5% of the total genetic variance in prostate cancer risk, with individual SNPs explaining 0.2-0.9% of variance.

This functional study identified 60 candidate differential allele-specific expression (DASE) loci in normal breast mammary epithelial cells using genome-wide SNP array analysis and validated them through Sanger sequencing. Key findings include identification of DMBT1 rs2981745 as a causal variant for DASE (DASE=2.03, P=0.0017, FDR=0.014), along with cancer-related genes ZNF331 and USP6 in a breast cancer-relevant pathway network. The study demonstrates that global DASE analysis is a novel approach for identifying breast cancer risk alleles.

This methods paper presents a novel retrospective likelihood approach for estimating genotype relative risks from ascertained pedigrees, which adjusts for ascertainment bias by conditioning on the phenotypes of all pedigree members. The authors apply this method to 28 previously reported prostate cancer SNPs in Mayo Clinic pedigree data (469 affected men) and case-control samples (661 cases, 518 controls), demonstrating that relative risk estimates from pedigrees are consistent with odds ratios from case-control studies.

This comprehensive review examines genetic association studies on prostate cancer, discussing GWASs that have identified over 75 variants associated with PCa risk (as of February 2016), with major susceptibility regions at 8q24, 17q12, 17q24, 10q11, and 19q13. The paper also reviews candidate gene-based approaches targeting genes involved in androgen signaling, carcinogen metabolism, DNA repair, vitamin D signaling, inflammation, angiogenesis, and cellular adhesion, as well as regulatory RNA genes.

This study examined the relationship between 233 colorectal cancer (CRC) risk loci and overall survival in 1,926 patients with advanced CRC from clinical trials. Two SNPs significantly associated with survival under a recessive model were identified: rs117079142 (HR=2.79, 95% CI=1.70-4.58, P=4.7×10⁻⁵) mapping to UTP23/EIF3H, and rs9924886 (HR=1.24, 95% CI=1.12-1.38, P=5.2×10⁻⁵) mapping to CDH1/CDH3. Low CDH1 gene expression in tumors was associated with worse survival (HR=2.18, P=1.8×10⁻³), supporting a prognostic role for CDH1 variants.

This case-control study examined whether seven breast cancer susceptibility alleles (in FGFR2, TNRC9, MAP3K1, LSP1, and chromosomal regions 8q24 and 2q35) were associated with epithelial ovarian cancer risk. The pooled analysis of 1,383 ovarian cancer cases and 1,804 controls found no significant associations between these variants and ovarian cancer risk, with OR estimates for FGFR2 rs1219648 of 1.06 (95% CI=0.95-1.18) and rs2981582 of 1.04 (95% CI=0.93-1.15), suggesting that breast cancer risk alleles may be specific to breast cancer.

A population-based case-control study tested whether five SNPs at chromosomal regions 8q24, 17q12, and 17q24.3, combined with family history, predict prostate cancer risk and mortality in Caucasians from King County, Washington (1,308 cases, 1,266 controls). Combined SNP genotypes and family history were significantly associated with prostate cancer risk (p trend = 1.5 × 10⁻²⁰), with men carrying ≥5 risk factors showing OR of 4.9 (95% CI 1.6–18.5). However, these factors did not improve prediction models after accounting for known risk predictors and were not associated with prostate cancer-specific mortality.

This review examines statistical and computational approaches for identifying functional single-nucleotide substitutions in cancer, including frequency-based methods for identifying highly mutated genes in cancer sequencing studies and bioinformatics approaches for predicting the functional impact of non-synonymous mutations and polymorphisms. The paper discusses both somatic mutations in cancer (driver vs. passenger mutations) and germline variants identified through GWAS, with emphasis on methods for analyzing amino acid changes, regulatory SNPs (such as rs6983267 associated with colorectal cancer), and non-coding mutations.

This case-case study of 5,895 prostate cancer patients from Johns Hopkins Hospital examined 20 genome-wide association study (GWAS)-identified risk SNPs for association with clinicopathologic variables of cancer aggressiveness. Only rs2735839 in KLK3 (p = 8.4 × 10⁻⁷) and rs10993994 in MSMB (p = 0.046) showed significant associations, but notably with the risk alleles being more frequent in less aggressive rather than more aggressive disease, likely reflecting PSA detection bias. The vast majority of the 20 tested SNPs showed no association with Gleason score, tumor stage, or aggressive disease phenotypes, suggesting they identify overall prostate cancer risk rather than aggressiveness.

This case-control study of 596 prostate cancer cases and 567 controls tested 49 tagging SNPs in the 8q24 region for association with prostate cancer susceptibility and tumor aggressiveness in men of European ancestry. After multiple testing correction, four SNPs showed significant association with PC susceptibility (rs1016342, rs1378897, rs871135, rs6470517), while rs6470517 was significantly associated with aggressive tumor phenotypes (Gleason score and TNM staging, P = 10^-4 to 10^-5). Meta-analysis of rs1447295 showed a pooled odds ratio of 1.38 (95% CI: 1.30-1.46).

This case-control study of 481 Japanese colorectal cancer patients and 962 controls found that the 8q24 variant rs6983267 is significantly associated with increased colorectal cancer risk (allelic OR = 1.22, 95% CI 1.04-1.44, p = 0.014), consistent with prior GWAS findings in other populations. The association remained significant after adjustment for lifestyle factors including smoking, alcohol consumption, folate intake, and BMI (adjusted OR = 1.25). The variant rs10090154 in the same locus did not show significant association.

This case-control study investigated 15 SNPs at the 8q24 locus for association with testicular germ cell tumors (TGCT) using 568 cases and 680 controls from the STEED military study. Overall, no significant associations were found between 8q24 SNPs and TGCT risk. However, nonseminomas showed three tentative associations: rs6470494 (OR=1.68 for GG genotype, p=0.04), rs13254738 (OR=1.62 for TT genotype, p=0.07), and an inverse association with rs10505476 (OR=0.67 for CT genotype, p=0.04).

This comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.

Family-based association study of 1,015 non-Hispanic white men from 403 familial and early-onset prostate cancer families examining chromosome 8q24 markers. rs6983561 (minor 'C' allele, OR=2.26) and rs6983267 (major 'G' allele, OR=1.30) showed significant associations with prostate cancer risk. rs6983561 was specifically associated with early-onset disease (age <50, p=0.03) with OR=4.69, while rs6983267 was associated with clinically aggressive disease (p=0.007) with OR=1.90.

This study confirms a strong cumulative effect of five genetic variants on prostate cancer risk across three populations: CAPS (Swedish), Johns Hopkins Hospital (JHH), and CGEMS-prostate (U.S.). Men carrying combinations of 1, 2, 3, and 4+ risk alleles had odds ratios of 1.41 (1.20-1.67), 1.88 (1.59-2.22), 2.36 (1.95-2.85), and 3.80 (2.77-5.22) respectively. When family history was included as a sixth risk factor, the cumulative effect was even stronger, with men carrying 5+ risk factors showing OR of 11.26 (4.74-24.75).

This comprehensive resequence analysis of a 136 kb region of chromosome 8q24 (chr8: 128,473,000-128,609,802) using 454 next-generation sequencing identified 442 novel SNPs and characterized the complete catalog of common variation across regions previously associated with prostate and colorectal cancer risk by GWAS. The study identified 780 common SNPs, with 454 having MAF ≥5%, and determined that 114 tag SNPs are necessary to comprehensively tag the region (r² > 0.8), providing important resources for fine-mapping association signals marked by rs6983267 and rs1447295.

This systematic review identified 53 unique SNPs in 29 genomic loci associated with aggressive prostate cancer progression and poor outcomes from GWAS studies. Functional studies implicated 21 SNPs as modulating the androgen receptor pathway, MYC oncogene, and PSA-related genes, with rs1447295 and rs10993994 being replicated across multiple populations and associated with unfavorable pathological features in low-grade prostate cancer.